Protein kinases are important in cellular signal pathways that regulate various cell functions, including differentiation, proliferation, migration, and apoptosis. Deregulation of protein kinases is implicated in cancer and a number of other diseases.
Heterocyclic compounds have been extensively studied as potent protein kinase inhibitors. Among various classes of heterocyclic compounds, aminothiazoles appear as a recurring structural motif in many biologically active compounds.
As drug candidates, aminothiazoles present several challenges. First, they generally lack adequate in vivo exposure to exert desirable efficacy in pre-clinical or clinical studies. Further, being promiscuous protein kinase inhibitors, aminothiazoles possess poor kinase selectivity. Moreover, they often cause animal death in toxicity studies, raising safety concerns.
There is a need to develop new aminothiazoles that effectively inhibit certain protein kinases, exert sufficient in vivo efficacy in treating target diseases, and demonstrate desirable safety profiles.